Using female sheep as the experimental model, this amended proposal will test the hypothesis that normally occurring changes in FSH heterogeneity are of functional significance , with increases in biopotency associated with the onset of puberty and the preovulatory period. The goals are to: (1) establish the modulatory role of estradiol in mediating FSH heterogeneity, (2) determine nature of FSH isoforms secreted during different phases of puberty and ovulatory cyclicity. (3) reveal the role of FSH heterogeneity in the initiation of the pubertal process through administration of different isoform mixes of recombinant-produced FSH to immature GnRH antagonist-treated lambs and (4) establish if freshly secreted non-metabolized, FSH isoforms in hypothalamo-pituitary portal plasma can effect different biological responses at the target site.